Current theories of drug abuse view addiction as a disease, but inevitably, the element of volitional choice will remain one of the key components of the illness. The issue boils down to this: why does an individual choose to use drugs even when they know about the negative consequences? To answer this question, we propose an experimental approach based on techniques and theories that have developed out of the field of neuroeconomics. This approach uses neuroimaging to uncover the relationships of otherwise unobservable variables in the brain that correspond to specific decisions that individuals make. Current evidence supports the theory that the orbitofrontal-striatal circuit encodes variables that relate to the economic idea of expected utility. The vast majority of these neuroeconomic studies, however, have focused on the domain of "gains." Many real-life decisions, such as the choice of whether or not to use drugs, however, also involve the potential for "loss." It is not currently known how the brain integrates decisions that involve both gains and losses. In this proposal, we will test two competing hypotheses: 1) the brain has a signed, one-dimensional system that computes the expected value of outcomes relative to some reference;or 2) the brain uses at least two different systems to compute, separately, gains and losses. To test these hypotheses, we propose 3 aims: 1) Determine the neural circuits involved in decision-making under 3 conditions: a) gains only;b) losses only;and c) gains and losses simultaneously. 2) Determine whether the circuits identified in the first aim are robust with respect to the medium of gain or loss. We will directly compare financial gains and losses with non-financial ones to test the hypothesis that a common neural "currency" is used as a measure of value for decision-making. 3) For the problem of addiction, decisions to use drugs almost always involve costs to other people as well as the individual. Using both a modified dictator game and variant of the prisoner's dilemma, we will determine whether decision-making that affects others'payoffs is also mediated by a common neural-currency hypothesis, or whether payoffs in terms of externalities on others invokes additional neural circuitry. PUBLIC HEALTH RELEVANCE: Why does an individual choose to use drugs even when they know about the negative consequences? To answer this question, we will use brain imaging to measure the brain's responses when an individual makes decisions that involve a variety of negative outcomes.